Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear.
Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
Conclusion: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
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http://dx.doi.org/10.4093/dmj.2023.0342 | DOI Listing |
Diabet Med
December 2024
Department of Biomolecular Pharmacology, Hoshi University, Tokyo, Japan.
Aims: Skin disorders occur more frequently with sodium-dependent glucose cotransporter type 2 (SGLT2) inhibitors than with other antidiabetic drugs. We conducted basic research using ipragliflozin, with the aim of identifying new measures to prevent skin disorders caused by SGLT2 inhibitors.
Methods: db/db type 2 diabetes model mice were orally administered ipragliflozin (10 mg/kg or 30 mg/kg) once a day for 28 days and skin function genes were analysed by real-time RT-PCR or Western blotting.
Cardiovasc Diabetol
December 2024
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
AntiCancer, Inc., San Diego, CA, USA.
Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells from mouse and human have been shown to differentiate into neurons, glia, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes in vitro. HAP stem cells have promoted the recovery of peripheral nerve and spinal cord injuries in mouse models by differentiating into glial fibrillary acidic protein (GFAP)-positive Schwann cells. HAP stem cells enclosed on polyvinylidene fluoride membranes (PFM) were transplanted into the severed thoracic spinal cord of nude mice.
View Article and Find Full Text PDFDiabetol Metab Syndr
December 2024
NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China.
Objectives: Among all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic environment is the lysis of renal resident cells.
View Article and Find Full Text PDFDiabetol Metab Syndr
December 2024
Shanghai Innogen Pharmaceutical Co., Ltd, Shanghai, China.
Background: Glucagon-like peptide 1 (GLP-1) is an incretin hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic agent. We demonstrated previously that supaglutide, a novel long-acting GLP-1 analog, exerted hypoglycemic, hypolipidemic, and weight loss effects in type 2 diabetic db/db mice, DIO mice, and diabetic monkeys.
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